This R34 application is designed to move our innovative treatment approach to improving cognition in schizophrenia from the feasibility stage to the pilot intervention trial stage. We propose a randomized controlled 6-month trial of the efficacy of a novel intervention combining neuroplasticity-based cognitive training with neurotrophin-releasing aerobic exercise, compared to the same cognitive training alone. Both of these treatments address the NIMH Strategic Plan and NIMH Director Tom Insel's request to create innovative interventions that can be disseminated broadly and readily taught to the existing workforce with minimal cost. The primary treatment targets are overall cognitive deficit level and impairment in independent living skills. A secondary outcome variable will be a key neurotrophic growth factor, brain-derived neurotrophic factor (BDNF). We hypothesize that combining neuroplasticity-based computerized cognitive training and neurotrophin-enhancing physical exercise will produce large cognitive and functional improvements, even relative to cognitive training alone. Based on theoretical considerations and our initial pilot data, the new cognitive training plus aerobic exercise intervention has the potential to make a real difference in the lives of individuals with severe mental illness. Adding aerobic exercise to our cognitive training program will have the additional benefit of helping to ameliorate medication side effects, reduce the risk for developing metabolic syndrome, and help to prevent the deterioration in physical health that usually follows the onset of schizophrenia and its pharmacologic treatment. Cognitive deficits in persons with schizophrenia present an enormous challenge when helping them to return to functioning in the community. Cognitive remediation and physical exercise have each been shown separately to have promise for improving cognitive deficits in schizophrenia, but used separately yield moderate effects. Our initial pilot data suggest that integrating these two interventions produces larger cognitive gains than the cognitive training alone. We posit that the increases in neurotrophic factors associated with regular aerobic exercise provide a platform which allows neuroplasticity-based cognitive training to impact cognition to a greater degree than is typically observed in studies of cognitive training alone. We target the period shortly after a first episode of schizophrenia to maximize the generalization of cognitive improvement to functional outcome, before chronic disability is established.